EGFR (epidermal growth factor receptor, referred to as EGFR, HER1 or ErbB-1) is a member of the epidermal growth factor receptor (HER) family, which play an important role in cell physiology. EGFR is a tyrosine kinase receptor, whose signal pathway plays an important regulatory role in cell proliferation, growth, differentiation, etc., and of which the abnormal expression or mutation usually leads to tumor.
Small molecule tyrosine kinase inhibitors prevent the interaction of ATP and receptor kinases, block the induction of intracellular kinase autophosphorylation led by ligand-receptor binding, and block the cross-phosphorylation triggered by dimerization of EGFR receptors, thereby block downstream signaling pathways, and is highly efficient and specific by the competitive binding of tyrosine kinase phosphorylation sites in the intracellular domain of EGFR.
The use of first-generation reversibly binding tyrosine kinase inhibitors, such as Gefitinib and Erlotinib, are susceptible to acquired resistance. Michael J. Eck et al. has found that this resistance is mainly due to the T790M mutation occurred in the gatekeeper residue of ErbB1, and this mutation produces resistance by enhancing the affinity of ATP and EGFR tyrosine kinases.
In 2009, Wenjun Zhou et al. discovered novel mutant selective small molecule inhibitors, such as WZ4002 and WZ8040:

Emily J. Hanan et al. obtained new kinase inhibitors through the cyclization strategy:

Kwangho Lee et al. also developed a series of EGFR kinase inhibitors (US2012157426) based on this and found that I-1 has very good inhibitory activity:

They further designed compound I-4 (KR20130133202, CN103269704):

Since EGFR inhibitors have important applications in the treatment of tumors, there is an urgent need in the art to develop drugs having tyrosine kinase inhibitory activity.